Osteoporosis and fragility fractures affect 40-50 percent of patients who have had organ transplantation. Improved survival of transplant recipients and expansion of transplantation programs make it likely that the incidence of transplantation osteoporosis will grow substantially. Over the past five years, new insights have been gained into the natural history, demographic and biochemical features of bone loss and fracture after cardiac transplantation, many of which are applicable to other types of organ transplantation. It is now known that the significant declines in lumbar spine and hip bone density (8-10 percent) and fractures (25-40 percent) occur primarily during the initial 6-12 months after transplantation. Although women, older patients and those with low pretransplant bone mass are at increased risk, men also fracture frequently. Moreover, many patients fracture despite normal pretransplant bone density. The early post-transplant period is characterized by increases in markers of bone resorption and decreases in both serum 1,25(OH)2vitamin D and osteocalcin, a marker of bone formation, all of which are associated with more rapid rates of cancelleous bone loss. The purpose of this proposal is to use these data to design a rational approach to the prevention of bone loss and fractures after transplantation. The specific aims of the proposal are to evaluate the efficacy and safety of the active metabolite of vitamin D, 1,25(OH)2D (calcitriol) and the antiresorptive bisphosphonate drug, alendronate, in the prevention of bone loss at the spine and hip after cardiac transplantation; to characterize the effects of these drugs on biochemical indices of bone and mineral metabolism during the first year after cardiac transplantation; and to establish the incidence of vertebral fracture during the first year after cardiac transplantation in patients treated with either calcitriol or alendronate. These specific aims will be addressed in a prospective, double-blind, design in which approximately 120 cardiac recipients at Columbia-Presbyterian Medical Center will be randomized shortly after transplantation to receive either A. active alendronate and placebo calcitriol or B. placebo alendronate and active calcitriol for the duration of the first post-transplant year. The goals of the study will be accomplished using timed serial measurements of bone density (spine and hip; by DEXA), spine radiographs and biochemical assays of calciotropic hormones and bone turnover markers. It is expected that this research will lead to rational programs for prevention of this crippling form of osteoporosis.